Chemical mixtures: challenge for toxicology and risk assessment.


:It is now well-recognized that human environmental exposures are not to single chemicals. Rather, humans are exposed, either concurrently or sequentially, to multiple chemicals. Challenges that chemical mixtures pose for risk assessment and toxicology are presented. Challenge areas include increasing the peer-reviewed publication of human studies, improving access to peer-reviewed data and examining multiple target organs. Two difficult challenges are development of a common, consistent language and the use of appropriate and innovative experimental designs and analyses. The challenge of elucidation of mechanism(s) offers a rational basis for extrapolation across dose levels, exposure durations and exposure routes as well as to other species and to other similar chemicals. Of particular importance is focusing effort on those areas of investigation where answers have the greatest potential for reducing uncertainty in risk assessments for chemical mixtures and on those chemical mixtures and multiple chemical exposures that have the greatest potential impact on human health. A particularly fruitful area for future investigation is determination of the likelihood of nonadditive interactions in humans exposed to multiple chemicals at environmental exposure levels.






Simmons JE




Has Abstract


1995-12-28 00:00:00














  • A two-centre study for the evaluation and validation of an animal model for the assessment of the potential of small molecular weight chemicals to cause respiratory allergy.

    abstract::This study evaluated a single intradermal injection model in the guinea pig with subsequent inhalation challenge and serological analysis as a method to predict the potential of chemicals to induce respiratory allergy. Four known respiratory allergens (trimellitic anhydride, diphenyl methane diisocyanate, phthalic anh...


    pub_type: 杂志文章,多中心研究


    authors: Blaikie L,Morrow T,Wilson AP,Hext P,Hartop PJ,Rattray NJ,Woodcock D,Botham PA

    更新日期:1995-01-19 00:00:00

  • Sodium valproate induces mitochondrial respiration dysfunction in HepG2 in vitro cell model.

    abstract::Sodium valproate (VPA) is a potentially hepatotoxic antiepileptic drug. Risk of VPA-induced hepatotoxicity is increased in patients with mitochondrial diseases and especially in patients with POLG1 gene mutations. We used a HepG2 cell in vitro model to investigate the effect of VPA on mitochondrial activity. Cells wer...


    pub_type: 杂志文章


    authors: Komulainen T,Lodge T,Hinttala R,Bolszak M,Pietilä M,Koivunen P,Hakkola J,Poulton J,Morten KJ,Uusimaa J

    更新日期:2015-05-04 00:00:00

  • Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity.

    abstract::Hesperidin (HDN) is a flavanone glycoside abundantly found in citrus fruits. HDN has been reported to possess significant activities against allergy, haemorrhoids, hormonal disorders and ulcers. Other reported activities include anti-inflammatory, analgesic, antibacterial, antifungal, antiviral, antioxidant and free r...


    pub_type: 杂志文章


    authors: Kaur G,Tirkey N,Chopra K

    更新日期:2006-09-21 00:00:00

  • The developmental toxicity of uranium in mice.

    abstract::To evaluate the developmental toxicity of uranium, 5 groups of 20 pregnant Swiss mice were given by gavage daily doses of 0, 5, 10, 25 and 50 mg/kg of uranyl acetate dihydrate on gestational days 6-15. Cesarean sections were performed on all females on gestation day 18. Fetuses were examined for external, visceral, an...


    pub_type: 杂志文章


    authors: Domingo JL,Paternain JL,Llobet JM,Corbella J

    更新日期:1989-04-01 00:00:00

  • Effects of molybdate and pentachlorophenol on the sulfation of acetaminophen.

    abstract::Pentachlorophenol (PCP) is an inhibitor of phenol-sulfotransferases and has been used to ascertain the role of sulfation in toxicology. Recently, molybdate has been shown to inhibit the sulfation of various chemicals by decreasing hepatic concentrations of the cosubstrate, 3'-phosphoadenosine 5'-phosphosulfate (PAPS)....


    pub_type: 杂志文章


    authors: Boles JW,Klaassen CD

    更新日期:2000-04-20 00:00:00

  • Induction and inhibition of cytochrome P-450-dependent monooxygenases in hamster tissues by ethanol.

    abstract::The effects of ethanol on hamster hepatic and extrahepatic monooxygenases were determined in the present study. Chronic ethanol administration increased cytochrome P-450 (P-450) content and monooxygenase activities towards aniline, N-nitrosodimethylamine, and 7-ethoxyresorufin. In contrast, benzphetamine and benzo(a)p...


    pub_type: 杂志文章


    authors: Ueng TH,Ueng YF,Tsai JN,Chao IC,Chen TL,Park SS,Iwasaki M,Guengerich FP

    更新日期:1993-07-28 00:00:00

  • Metabolism of benzo[a]pyrene in the combined rat liver--lung perfusion system.

    abstract::The influence of the insertion of a liver into the perfusion circuit of a lung on the availability of benzo[a]pyrene and benzo[a]pyrene metabolites to the lung was examined. Perfused lungs from 5,6-benzoflavone pretreated rats release high quantities of free benzo[a]pyrene metabolites and conjugates into the perfusion...


    pub_type: 杂志文章


    authors: Mollière M,Foth H,Kahl R,Kahl GF

    更新日期:1987-08-01 00:00:00

  • Formation of hydrogen fluoride by gamma and beta sterilisation in medical devices containing perfluoroheptane.

    abstract::Infusion of hexadecafluoroheptane, a liquid perfluorocarbon released from repaired Althane dialysers was found to be the most probable reason for the deaths of 53 dialysis patients reported in the year 2001. This study focuses on toxic decomposition products generated due to gamma and beta sterilisation of hexadecaflu...


    pub_type: 杂志文章


    authors: Zündorf J,Kremer S,Grüger T

    更新日期:2008-01-20 00:00:00

  • An assessment of the ability of phthalates to influence immune and allergic responses.

    abstract::It has been suggested that one possible contributor to the increasing prevalence of atopic (IgE-mediated) allergic diseases and asthma in Europe and the US is exposure to chemicals that may act as adjuvants. Certain commonly used phthalate plasticisers, such as di-(2-ethylhexyl) phthalate, have been implicated in this...


    pub_type: 杂志文章,评审


    authors: Kimber I,Dearman RJ

    更新日期:2010-05-27 00:00:00

  • 1,3-Dinitrobenzene metabolism and toxicity in seminiferous tubules isolated from rats of different ages.

    abstract::Previous in vivo studies in rats have shown that susceptibility to 1,3-dinitrobenzene (DNB)-induced testicular damage increases with age. The present study has used an in vitro approach to investigate the possibility that differences in testicular metabolism contribute to the age-related differences in toxicity. Semin...


    pub_type: 杂志文章


    authors: Jacobson CF,Miller MG

    更新日期:1997-11-21 00:00:00

  • Differences in the H2S-induced quantal release of catecholamine in adrenal chromaffin cells of neonatal and adult rats.

    abstract::Both catecholamine (CA) released from adrenal chromaffin cells and hydrogen sulfide (H2S) have been shown to play critical roles in the regulation of hypoxic stress response. Our previous study has demonstrated that exogenous H2S directly induced quantal CA released from adult rat adrenal chromaffin cells (ARACCs) by ...


    pub_type: 杂志文章


    authors: Wang K,Zhu D,Yu X,Sun J,Yao W

    更新日期:2013-10-04 00:00:00

  • Investigations of protective effects of the flavonoids quercetin and rutin on stress resistance in the model organism Caenorhabditis elegans.

    abstract::Oxidative stress as a result of excessive generation of reactive oxygen species (ROS) or diminished antioxidative defence is regarded as a main factor in the pathophysiology of various diseases and ageing. Many flavonoids that are present in herbal edibles have antioxidative properties and possess a remarkable spectru...


    pub_type: 杂志文章


    authors: Kampkötter A,Nkwonkam CG,Zurawski RF,Timpel C,Chovolou Y,Wätjen W,Kahl R

    更新日期:2007-05-05 00:00:00

  • Different levels of Schistosoma mansoni infection increased the mutagenicity of benzo(a)pyrene, the activity of aryl hydrocarbon hydroxylase and the formation of hepatic microsomal hydrogen peroxide.

    abstract::The present study investigates the influence of different levels of Schistosoma mansoni infection (60, 120, 180, 300, 600 cercariae per mice) after 33 days on the activity of aryl hydrocarbon hydroxylase (AHH) and the formation of hepatic hydrogen peroxide (H(2)O(2)) during the metabolic activation of benzo(a)pyrene [...


    pub_type: 杂志文章


    authors: Awney HA,Ghzlan HE,Sheweita SA,Mostafa MH

    更新日期:2001-06-21 00:00:00

  • The oxidative stress-induced niacin sink (OSINS) model for HIV pathogenesis.

    abstract::Although several specific micronutrient deficiencies are associated with disease progression and increased mortality risk in HIV/AIDS, and even a simple multivitamin/mineral supplement can prolong survival, this is typically viewed merely as nutritional support of the immune system, and only necessary if there are def...


    pub_type: 杂志文章


    authors: Taylor EW

    更新日期:2010-11-28 00:00:00

  • Low level prenatal exposure to methylmercury disrupts neuronal migration in the developing rat cerebral cortex.

    abstract::We determined the effects of low-level prenatal MeHg exposure on neuronal migration in the developing rat cerebral cortex using in utero electroporation. We used offspring rats born to dams that had been exposed to saline or various doses of MeHg (0.01 mg/kg/day, 0.1 mg/kg/day, and 1 mg/kg/day) from gestational day (G...


    pub_type: 杂志文章


    authors: Guo BQ,Yan CH,Cai SZ,Yuan XB,Shen XM

    更新日期:2013-02-08 00:00:00

  • Renal and hepatic nucleic acid metabolism in neonates: relation to experimental duration, chlorphentermine dose as well as subsequent withdrawal.

    abstract::Daily oral administration of either 20, 40 or 60 mg/kg chlorphentermine for 7 days significantly increased liver and kidney DNA levels, which were not elevated further even after a 3 week treatment period. Although cessation of drug administration for 3 weeks resulted in a return of hepatic DNA levels to control value...


    pub_type: 杂志文章


    authors: Kacew S,Dubas TC,Stevenson AJ

    更新日期:1978-05-01 00:00:00

  • Chlordecone potentiation of CCl4 hepatotoxicity in ovariectomized rats.

    abstract::Previous reports from this laboratory have established the propensity of chlordecone to potentiate the hepatotoxicity and lethality in male and female rats. The present study was designed to investigate the hepatotoxicity of CCl4 in chlordecone (CD) pretreated, ovariectomized rats. Ten days after bilateral ovariectomy...


    pub_type: 杂志文章


    authors: Agarwal AK,Mehendale HM

    更新日期:1984-02-01 00:00:00

  • Effects of ethanol in acute carbon monoxide poisoning.

    abstract::The combined effects of ethyl alcohol (ETOH) intoxication and carbon monoxide (CO) poisoning were studied in the Levine-prepared rat. Infusion or injection of ETOH before and during 90 min of CO exposure to blood levels 2-4 times those considered legally drunk in humans, increased survival at 2400 ppm, and extended th...


    pub_type: 杂志文章


    authors: Sharma P,Penney DG

    更新日期:1990-05-31 00:00:00

  • Uptake of carbon monoxide in blood of miniture pigs and other mammals.

    abstract::Different affinities of blood for CO were observed in in vivo and in vitro experiments. Hamsters showed the greatest relative affinity (1.0), the corresponding value for rats was 0.8, for pigs 0.74 and for rabbits 0.58. The upward shift of the saturation curves was dependent on the rate of respiratory exchange per uni...


    pub_type: 杂志文章


    authors: Klimisch HJ,Chevalier HJ,Harke HP,Dontenwill W

    更新日期:1975-01-01 00:00:00

  • Low molecular weight thiols reduce thimerosal neurotoxicity in vitro: modulation by proteins.

    abstract::Thimerosal (TH), an ethylmercury complex of thiosalicylic acid has been used as preservative in vaccines. In vitro neurotoxicity of TH at high nM concentrations has been reported. Although a number of toxicological experiments demonstrated high affinity of mercury to thiol groups of the extracellular amino acids and p...


    pub_type: 杂志文章


    authors: Zieminska E,Toczylowska B,Stafiej A,Lazarewicz JW

    更新日期:2010-10-29 00:00:00

  • Aspartame: review of recent experimental and observational data.

    abstract::In this report the neurotoxicity of aspartame and its constituent amino acids aspartic acid and phenylalanine is reviewed. The adverse reactions ascribed to the consumption of aspartame-containing products, as reported in the U.S.A., are discussed and placed in perspective with the results of recent behavioural studie...


    pub_type: 杂志文章,评审


    authors: Janssen PJ,van der Heijden CA

    更新日期:1988-06-01 00:00:00

  • Muscle force and acetylcholinesterase activity in mouse hemidiaphragms exposed to paraoxon and treated by oximes in vitro.

    abstract::The therapy of organophosphorus compound (OP) poisoning is still a challenge to clinical toxicologists. To alleviate peripheral respiratory failure oximes, e.g. obidoxime and pralidoxime, are used to reactivate inhibited acetylcholinesterase (AChE) with the intention to restore the disturbed neuromuscular function. In...


    pub_type: 杂志文章


    authors: Thiermann H,Eyer P,Worek F

    更新日期:2010-06-04 00:00:00

  • Methodology of forensic neurotoxicity evaluation: PCB case.

    abstract::Many scientists and doctors are not aware that the level of certainty for litigation purposes differs from that usually associated with scientific studies. Although the 0.05 probability level is commonly used in scientific studies ("beyond a reasonable doubt"), in U.S. civil litigation the diagnostic criteria is "more...


    pub_type: 杂志文章


    authors: Singer R

    更新日期:1988-05-01 00:00:00

  • The interactions of cis-diamminedichloroplatinum with metallothionein and glutathione in rat liver and kidney.

    abstract::The involvement of metallothionein (MT) in the nephrotoxicity of cis-diamminedichloroplatinum (c-DDP) was investigated in rats using enzyme excretion and histology as indicators of renal damage. In addition, the effects of renal glutathione (GSH) depletion on the nephrotoxicity of c-DDP was assessed by organic anion t...


    pub_type: 杂志文章


    authors: Suzuki CA,Cherian MG

    更新日期:1990-11-01 00:00:00

  • Expression of MRP1 and related transporters in human lung cells in culture.

    abstract::Multidrug resistance type 1 P-glycoproteins (P-gp) and multidrug resistance associated proteins (MRP) were studied in differentiated primary human lung cells in culture, in comparison with permanent human lung cell lines and primary alveolar type II cells from rat lung. AII cells exhibited low basal levels of mdr1b mR...


    pub_type: 杂志文章


    authors: Lehmann T,Köhler C,Weidauer E,Taege C,Foth H

    更新日期:2001-10-05 00:00:00

  • Cultured human peripheral blood mononuclear cells alter their gene expression when challenged with endocrine-disrupting chemicals.

    abstract::Endocrine disrupting chemicals (EDCs) have the potential to interfere with the hormonal system and may negatively influence human health. Microarray analysis was used in this study to investigate differential gene expression in human peripheral blood cells (PBMCs) after in vitro exposure to EDCs. PBMCs, isolated from ...


    pub_type: 杂志文章


    authors: Wens B,De Boever P,Verbeke M,Hollanders K,Schoeters G

    更新日期:2013-01-07 00:00:00

  • A study of the embryotoxicity of the food colour Ponceau 4 R in rats.

    abstract::An embryotoxicity study on Ponceau 4 R was carried out in SPF Wistar rats. The substance was given by gavage from day 1 to 20 of the gestation period in doses of 0, 1000, 2000, and 4000 mg/kg bw per day, dissolved in distilled water. The foetuses were removed on day 21. No effect due to the treatment with the dye was ...


    pub_type: 杂志文章


    authors: Meyer O,Hansen EV

    更新日期:1975-11-01 00:00:00

  • Maternal protein-and-energy restriction reduces the developmental toxicity of cyclophosphamide and hydroxyurea in rats.

    abstract::In this study, we examined the relationship between maternal weight gain deficits induced by protein-and-energy restriction (PER) and pregnancy outcome. We also evaluated whether PER would potentiate the developmental toxicity of cyclophosphamide (CP) and hydroxyurea (HU). Two independent experiments--employing two di...


    pub_type: 杂志文章


    authors: Chahoud I,Kuriyama SN,Paumgartten FJ

    更新日期:2002-09-30 00:00:00

  • The optimization test in the guinea pig in relation to other predictive sensitization methods.

    abstract::The allergenicity of various compounds was tested by means of the optimization procedure in the guinea-pig. Results with antibiotics, preservatives, fragrance raw materials and miscellaneous contactants are reported. Their relevance is critically discussed in relation to other animal sensitization methods (Draize, Büh...


    pub_type: 杂志文章


    authors: Maurer T,Weirich EG,Hess R

    更新日期:1980-01-01 00:00:00

  • Sodium benzoate attenuates D-serine induced nephrotoxicity in the rat.

    abstract::D-Serine causes selective necrosis to the straight portion of the rat renal proximal tubules. The onset is rapid, occurring within 3-4 h and accompanied by proteinuria, glucosuria and aminoaciduria. The metabolism of D-serine by D-amino acid oxidase (D-AAO) may be involved in the mechanism of toxicity. D-AAO is locali...


    pub_type: 杂志文章


    authors: Williams RE,Lock EA

    更新日期:2005-02-01 00:00:00